An essential role for HLA–DM in antigen presentation by class II major histocompatibility molecules

• Published in: Nature (London) 1994-04, Vol.368 (6471), p.551-554
• Main Authors: Morris, Phillip, Shaman, Jeffrey, Attaya, Michelle, Amaya, Miguel, Goodman, Steven, Bergman, Carolyn, Monaco, John J., Mellins, Elizabeth
• Format: Article
• Language: English
• Subjects: Animals; Antigen-Presenting Cells - physiology; B-Lymphocytes - immunology; B-Lymphocytes - physiology; Base Sequence; Cell Line; Genetics; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - physiology; HLA-D Antigens - genetics; HLA-D Antigens - physiology; Humanities and Social Sciences; Humans; Immunity (Disease); letter; Mice; Molecular Sequence Data; multidisciplinary; Mutation; Science; Science (multidisciplinary); Transfection
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/368551a0

IN antigen-presenting cells, class II molecules of the major histocompatibility complex (MHC) bind peptides derived from endo-cytosed proteins 1 . In certain B-lymphoblastoid cell mutants, MHC class II molecule–peptide complex formation is impaired, resulting in deficient antigen-presenting function 2 . MHC deletion mutants with this defect map the responsible gene(s) to the class II region of the MHC 3–5 . Here we report that multiple independent mutants with the class II presentation defect harbour lesions in HLA-DMB , an MHC-linked gene encoding a class II-like β-chain 6,7 . Expression of DMB complementary DNA in mutants lacking DMB messenger RNA restores the wild-type phenotype. These results establish HLA-DM as a critical regulatory molecule in class II-restricted antigen presentation and suggest that it functions at an intracellular site to promote class II molecule–peptide association.